Cancer is responsible for about one third of all mortalities in the United States, while metastatic disease is responsible for more than 90% of all cancer-related deaths (Sporn, Lancet 347:1377-1381, 1996). Cellular abnormalities have been organized into six basic competency traits that must be acquired for a malignancy to thrive: self-sufficiency in growth signals, insensitivity to anti-proliferative signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis (Hanahan and Weinberg, Cell 100:57-70, 2000). These competencies are thought to be the product of alterations attained by the tumor early in the clinical timeline. Coupled with the increasing heterogeneity of the tumor cell population over time, multiple phenotypes may arise with varying levels and tendencies of metastatic competency (Fidler, Nature Rev. Cancer 3:453-458, 2003).
Animal models have added to the current understanding of malignant and metastatic progression. The use of different models and techniques, such as in vivo passaging for phenotype purification, transgenic animals for specific molecular manipulation, and in vivo and ex vivo models for screening of cancer therapies has led to functional insights that have allowed development of useful models regarding the causes of malignancy and how to further investigate malignant behavior.
Another valuable and recent breakthrough over the past ten years has been the development and use of high throughput assays, such as microarray expression analysis. Molecular profiling with this technology has gained acclaim and some utility in the management of select cancer patients. Several gene expression-based assays are now marketed for improved prognostic accuracy for patients with breast cancer (Driouch et al., Clin. Exp. Metastasis 24:575-585, 2007).